Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility

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Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility.

BACKGROUND Sildenafil was recently approved for the treatment of pulmonary arterial hypertension. The beneficial effects of phosphodiesterase type 5 (PDE5) inhibitors in pulmonary arterial hypertension are thought to result from relatively selective vasodilatory and antiproliferative effects on the pulmonary vasculature and, on the basis of early data showing lack of significant PDE5 expression...

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Hypertrophied right hearts get two for the price of one: can inhibiting phosphodiesterase type 5 also inhibit phosphodiesterase type 3?

Phosphodiesterase type 5 (PDE5) was first discovered in the mid 1970s, not as a PDE but rather as a binding protein for cGMP.1 Shortly thereafter, it became clear that this protein also had cGMP-selective PDE activity, and cGMP-binding to domains in the N-terminus (GAF domains) regulated its enzymatic activity.2 PDE5 gained more attention in the mid 1980s when its role in modulating vascular to...

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Type 5 phosphodiesterase inhibition: the focus shifts to the heart.

Of the molecules that transmit an extracellular message to alter cardiomyocyte physiology, the cyclic nucleotides are among the better understood as regulators of cell function. The relatively recent identification of nitric oxide (NO) as a stimulus of cGMP production by soluble guanyl cyclase,1 as well as of the natriuretic peptides as a stimulating membrane-bound guanylate cyclase,2 has led t...

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Effect of regular phosphodiesterase type 5 inhibition in hypertension.

There are no published controlled clinical trials of regular phosphodiesterase type 5 inhibitor therapy as a long-term treatment of hypertension. In a randomized, double-blind, 2-way crossover study, 25 otherwise untreated hypertensive subjects were administered 50 mg of sildenafil or matched placebo 3 times daily for 16 days, and the effects on ambulatory blood pressure (BP), clinic BP, arteri...

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Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure.

ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelia...

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ژورنال

عنوان ژورنال: Circulation

سال: 2007

ISSN: 0009-7322,1524-4539

DOI: 10.1161/circulationaha.106.655266